Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Carbon dioxide and brain injury in preterm infants

Journal of Perinatology volume 41, pages 183–184 (2021)Cite this article

Subjects

Carbon dioxide is an important vasoactive agent associated with major outcomes among preterm infants including bronchopulmonary dysplasia, necrotizing enterocolitis, intracranial hemorrhage, periventricular leukomalacia, and death [1,2,3,4,5]. Secondary analysis of the SUPPORT trial data observed that fluctuations in carbon dioxide levels may be implicated in the development of severe intracranial hemorrhage among extremely preterm infants [3]. However, the randomized controlled trials and meta-analyses of respiratory support using CPAP with permissive hypercapnia did not report an increased risk of intracranial hemorrhage [4]. Thus, it is not known whether the association between carbon dioxide (pCO2) levels and brain injury [3] was due to confounding or due to changes in cerebral vascular flow among infants with impaired autoregulation. As permissive hypercapnia is now widely adopted, it is important to evaluate the effects of pCO2 on cerebral blood flow in the population at highest risk of intracranial hemorrhage due in part to impaired cerebral autoregulation [6].

In this edition of the Journal of Perinatology, Hoffman et al. reported associations between pCO2 and measures of cerebral perfusion [6]. Using prospective data from a sample of 61 very preterm infants, the authors reported changes in regional cerebral oxygenation (rScO2) using near-infrared spectroscopy (NIRS), as a surrogate measure of cerebral blood flow, and the association with pCO2 levels. There was a modest 5% increase in rScO2 with pCO2 levels above 55 mmHg but no correlation between rScO2–mean arterial pressure (MAP) and pCO2 indicating that cerebral autoregulation was not affected by pCO2 levels above 55 mmHg. The number of blood samples per patient ranged from 3 to 43 suggesting that the results of this study may have been disproportionately affected by a few infants who had more samples presumably due to clinical indications including illness severity or mode of respiratory support. Targeting cerebral NIRS and MAP is complex in extremely preterm infants. While this study controlled for respiratory support and vasopressor support, changes in rScO2–MAP can also be affected by small changes in FiO2, the use of normal saline bolus, glucose intake, PDA treatment, blood transfusion, and/or hematocrit, which may have confounded the results of this study [7]. Targeting NIRS resulted in a nonsignificant trend toward lower rates of mortality and severe intracranial hemorrhage among extremely preterm infants [8]. Data on optimal MAP targeting are lacking in this population.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Carlo WA, Stark AR, Wright LL, Tyson JE, Papile LA, Shankaran S, et al. Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants. J Pediatr. 2002;141:370–4. https://doi.org/10.1067/mpd.2002.127507.

    Article  PubMed  Google Scholar 

  2. Mariani G, Cifuentes J, Carlo WA. Randomized trial of permissive hypercapnia in preterm infants. Pediatrics. 1999;104:1082–8. https://doi.org/10.1542/peds.104.5.1082.

    Article  CAS  PubMed  Google Scholar 

  3. Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics. 2007;119:299–305. https://doi.org/10.1542/peds.2006-2434.

    Article  PubMed  Google Scholar 

  4. Rojas-Reyes MX, Morley CJ, Soll R. Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2012:CD000510. https://doi.org/10.1002/14651858.CD000510.pub2.

  5. Thome UH, Genzel-Boroviczeny O, Bohnhorst B, Schmid M, Fuchs H, Rohde O, et al. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Respir Med. 2015;3:534–43. https://doi.org/10.1016/S2213-2600(15)00204-0.

    Article  PubMed  Google Scholar 

  6. Hoffman SB, Lakhani A, Viscardi RM. The association between carbon dioxide, cerebral blood flow and autoregulation in the preterm infant. J Perinatol. 2020. https://doi.org/10.1038/s41372-020-00835-4.

  7. Riera J, Hyttel-Sorensen S, Bravo MC, Cabañas F, López-Ortego P, Sanchez, L, et al. The SafeBoosC phase II clinical trial: an analysis of the interventions related with the oximeter readings. Arch Dis Child Fetal Neonatal Ed. 2016;101:F333–8. https://doi.org/10.1136/archdischild-2015-308829.

    Article  PubMed  Google Scholar 

  8. Hyttel-Sorensen S, Greisen G, Als-Nielsen B, Gluud C. Cerebral near-infrared spectroscopy monitoring for prevention of brain injury in very preterm infants. Cochrane Database Syst Rev. 2017;9:CD011506. https://doi.org/10.1002/14651858.CD011506.pub2.

    Article  PubMed  Google Scholar 

  9. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010;362:1970–9. https://doi.org/10.1056/NEJMoa0911783.

    Article  PubMed Central  Google Scholar 

  10. Dunn MS, Kaempf J, de Klerk A, de Klerk R, Reilly M, Howard D, et al. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Pediatrics. 2011;128:e1069–76. https://doi.org/10.1542/peds.2010-3848.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Alabama at Birmingham, Birmingham, AL, USA

    Colm P. Travers & Waldemar A. Carlo

Authors
  1. Colm P. Travers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Waldemar A. Carlo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Waldemar A. Carlo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Travers, C.P., Carlo, W.A. Carbon dioxide and brain injury in preterm infants. J Perinatol 41, 183–184 (2021). https://doi.org/10.1038/s41372-020-00842-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-020-00842-5

This article is cited by

Search

Advanced search

Quick links